| Curcumin is the main active ingredient of the medicinal and edible plant, turmeric. It has good preventive and therapeutic effect against most of the clinical inflammation for its excellent anti-inflammatory activity in vitro and in vivo. The high oral doses of curcumin have no side effect on human body, which is of great significance for the development of new anti-inflammatory drugs and functional food. But curcumin has some disadvantages, including poor water solubility, low bioavailability and etc., which limit the development of curcumin-containing anti-inflammatory agents and functional food. Therefore, in this study, we used 3 typical carriers to solubilize the curcumin through the solid dispersion techniques, and evaluates the solubility, dissolution, stability, pharmacokinetic and anti-inflammatory activity of these 3 curcumin solid preparations. This study may provide theoretical foundation for the development of curcumin-containging drugs and functional food.In this study, we chose three typical solubilization carrier, PVP, Poloxamer and HP-β-CD, and prepared the curcumin solid preparations through the solvent method, The result showed that all 3 carriers enhance the solubility and dissolution of curcumin, and also improve the stability and tolerance of curcumin under the light, heat, alkali, metal ions and food additives. PVP showed the best improvement effect, Poloxamer the next. But the effect of HP-β-CD is not ideal.We use XRD, SEM, DSC and FTIR, Raman and 1H-NMR characterization techniques to study the solubilizing mechanism. The results showed that the crystal structure of curcumin was changed in to the amorphous or molecular form after carrier package dispersion. The solubilization mechanism may be as follows; PVP wrapped two curcumin molecules through the hydrogen-bond interaction The two molecules formed the hydrogen bond between the phenolic hydroxyl group and the methoxy group. Poloxamer took the curcumin as the center, and OH and H at the end of the chain wrap with the curcumin in phenolic hydroxyl group, enolic hydroxyl and methoxy group in the form of hydrogen bond. Curcumin enters the HP-β-CD cavity with a benzene ring. The results revealed different solubilization mechanisms of 3 preparations to some extent.We also studies pharmacokinetics experiment. Including Caco-2 cell membrane and bioavailability experiment. Results demonstrated that the carrier can improve the in vitro and vivo stability of curcumin, and promote the intestinal absorption of curcumin under the efficient transfer in cells, and significantly increase the blood concentrations of curcumin in vivo. The bioavailability of PV4 (curcumin:PVP in weight ratiol:9), PO4 (curcumin: Poloxamer in weight ratiol:9) and HP4 (curcumin:HP-β-CD in weight ratiol:9) in the curcumin solid preparation group increases by 11.13,3.94 and 1.30 times, respectively.Based on PV4 prescription showed good bioavailability, and further study anti-inflam-matory of PV4, The results show good anti-inflammatory of PV4 against TPA-induced rat ear swelling is 55.2%. The Paraffin section shows that the number of PV4 inflammation infiltrating cell is greatly decreased, which prevents the excessive cutin, inhibits the inflammatory cells proliferation and reduces the thickness of cuticle. It has the significant anti-inflammatory effect, tending to the blank group morphologically. To further invstigate anti-inflammatory mechanism of PV4, the result of ELISA experiments show that PV4 can significantly reduce TPA promote excessive expression of MMP-9, VEGF and IL-1β, and effectively reduce the level of MIP-2, TNF-a and IL-6, which suggested that the curcumin in PV4 may acts on the NF-κB pathway to inhibit the expression of downstream or secondary inflammatory factorsto playing the anti-inflammatory effect. |
PDF Full Text Request